Zhang Yinglei, Hu Chunyan, Niu Cong, Hong Jiaxu, Zhou Xujiao
Eye Institute, Eye & ENT Hospital, Fudan University, Shanghai 200032, China.
Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai 200032, China.
J Clin Med. 2023 Jan 29;12(3):1056. doi: 10.3390/jcm12031056.
To investigate whether asiatic acid (AA) can improve the quantity and function of retinal ganglion cells (RGCs), as well as how AA regulates synaptic pathways in rat models with chronic glaucoma.
In our study, a rat model of chronic glaucoma was prepared via the electrocoagulation of the episcleral veins. The numbers of surviving RGCs were counted via retrograde Fluorogold labeling, and a whole-cell patch clamp was used to clamp RGCs in normal retinal sections and in retinal sections 4 weeks after glaucoma induction.
Retrograde-Fluorogold-labeled RGC loss caused by persistent glaucoma was decreased by AA. Additionally, AA reduced the postsynaptic current produced by N-methyl-D-aspartate (NMDA) and diminished miniature glutamatergic excitatory neurotransmission to RGCs. On the other hand, AA increased miniature gamma-aminobutyric acid (GABA)-ergic inhibitory neurotransmission to RGCs and enhanced the GABA-induced postsynaptic current. The excitability of the RGC itself was also decreased by AA. RGCs in glaucomatous slices were less excitable because AA decreased their spontaneous action potential frequency and membrane potential, which led to a hyperpolarized condition.
AA directly protected RGCs in a chronic glaucoma rat model by lowering their hyperexcitability. To enhance RGCs' survival and function in glaucoma, AA may be a viable therapeutic drug.
研究积雪草苷（AA）是否能改善视网膜神经节细胞（RGCs）的数量和功能，以及AA如何调节慢性青光眼大鼠模型中的突触通路。
在我们的研究中，通过电凝巩膜静脉制备慢性青光眼大鼠模型。通过逆行荧光金标记计数存活的RGCs数量，并使用全细胞膜片钳在正常视网膜切片和青光眼诱导后4周的视网膜切片中钳制RGCs。
AA减少了持续性青光眼导致的逆行荧光金标记的RGC损失。此外，AA降低了由N-甲基-D-天冬氨酸（NMDA）产生的突触后电流，并减少了微小谷氨酸能兴奋性神经传递至RGCs。另一方面，AA增加了微小γ-氨基丁酸（GABA）能抑制性神经传递至RGCs，并增强了GABA诱导的突触后电流。AA还降低了RGC自身的兴奋性。青光眼切片中的RGCs兴奋性较低，因为AA降低了它们的自发动作电位频率和膜电位，导致超极化状态。
AA通过降低慢性青光眼大鼠模型中RGCs的过度兴奋性直接保护了它们。为了提高青光眼模型中RGCs的存活和功能，AA可能是一种可行的治疗药物。
